Skip to main content
Top
Published in: Breast Cancer Research and Treatment 2/2015

01-06-2015 | Clinical trial

Moderate level of HER2 expression and its prognostic significance in breast cancer with intermediate grade

Authors: Tanja Ignatov, Holm Eggemann, Elke Burger, Franziska Fettke, Serban Dan Costa, Atanas Ignatov

Published in: Breast Cancer Research and Treatment | Issue 2/2015

Login to get access

Abstract

Overexpression of human epidermal growth factor receptor 2 (HER2) is an important prognostic and predictive marker of response to anti-HER2 therapy in breast cancer. Our goal was to analyze the prognostic significance of moderate expression of HER2 in breast cancer with intermediate differentiation grade. We performed a multicenter retrospective register study of 8494 patients with primary non-metastatic breast cancer admitted between 2000 and 2011 to eight Clinics in Saxony-Anhalt, federal state of Germany. Patients were divided into three groups according to their HER2 score: 4073 were classified as HER2 negative (HER2 0 and 1+), 822 HER2 moderate (HER2 2+/HER2), and 1238 HER2 positive (HER2 3+ or HER2 2+/HER2+). HER2-positive cases were excluded from analysis. Tumors with moderate HER2 (HER2 2+) expression demonstrated an aggressive behavior and worse patient survival compared with HER2 0 and 1+ status. HER2 2+ status was associated with shorter median overall survival (OS) (P < 0.0001) in breast cancer patients with an intermediate grade of differentiation. Comparing low-grade and high-grade tumors, HER2 moderate expression did not significantly influence patient survival. In multivariate analysis after adjustment for other prognostic factors HER2 2+ status remained an unfavorable prognostic factor for OS (HR 1.224, 95 % CI 1.059–1.415, P = 0.006) in breast cancer patients with an intermediate grade of differentiation. HER2 2+ status is an unfavorable prognostic factor regarding the OS of breast cancer patients with intermediate grade of differentiation and could be used to identify patients, who may benefit from adjuvant therapy.
Literature
1.
go back to reference Aebi S, Davidson T, Gruber G, Castiglione M (2010) Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 21(Suppl 5):v9–14CrossRefPubMed Aebi S, Davidson T, Gruber G, Castiglione M (2010) Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 21(Suppl 5):v9–14CrossRefPubMed
2.
go back to reference Akiyama T, Sudo C, Ogawara H, Toyoshima K, Yamamoto T (1986) The product of the human c-erbB-2 gene: a 185-kilodalton glycoprotein with tyrosine kinase activity. Science 232:1644–1646CrossRefPubMed Akiyama T, Sudo C, Ogawara H, Toyoshima K, Yamamoto T (1986) The product of the human c-erbB-2 gene: a 185-kilodalton glycoprotein with tyrosine kinase activity. Science 232:1644–1646CrossRefPubMed
3.
go back to reference Barrett C, Magee H, O’Toole D, Daly S, Jeffers M (2007) Amplification of the HER2 gene in breast cancers testing 2+ weak positive by HercepTest immunohistochemistry: false-positive or false-negative immunohistochemistry? J Clin Pathol 60:690–693CrossRefPubMedCentralPubMed Barrett C, Magee H, O’Toole D, Daly S, Jeffers M (2007) Amplification of the HER2 gene in breast cancers testing 2+ weak positive by HercepTest immunohistochemistry: false-positive or false-negative immunohistochemistry? J Clin Pathol 60:690–693CrossRefPubMedCentralPubMed
4.
go back to reference Bedard PL, Hansen AR, Ratain MJ, Siu LL (2013) Tumour heterogeneity in the clinic. Nature 501:355–364CrossRefPubMed Bedard PL, Hansen AR, Ratain MJ, Siu LL (2013) Tumour heterogeneity in the clinic. Nature 501:355–364CrossRefPubMed
5.
go back to reference Berry DA, Muss HB, Thor AD, Dressler L, Liu ET, Broadwater G, Budman DR, Henderson IC, Barcos M, Hayes D, Norton L (2000) HER-2/neu and p53 expression versus tamoxifen resistance in estrogen receptor-positive, node-positive breast cancer. J Clin Oncol 18:3471–3479PubMed Berry DA, Muss HB, Thor AD, Dressler L, Liu ET, Broadwater G, Budman DR, Henderson IC, Barcos M, Hayes D, Norton L (2000) HER-2/neu and p53 expression versus tamoxifen resistance in estrogen receptor-positive, node-positive breast cancer. J Clin Oncol 18:3471–3479PubMed
6.
go back to reference Borg A, Tandon AK, Sigurdsson H, Clark GM, Ferno M, Fuqua SA, Killander D, McGuire WL (1990) HER-2/neu amplification predicts poor survival in node-positive breast cancer. Cancer Res 50:4332–4337PubMed Borg A, Tandon AK, Sigurdsson H, Clark GM, Ferno M, Fuqua SA, Killander D, McGuire WL (1990) HER-2/neu amplification predicts poor survival in node-positive breast cancer. Cancer Res 50:4332–4337PubMed
7.
go back to reference Buerger H, Mommers EC, Littmann R, Simon R, Diallo R, Poremba C, Dockhorn-Dworniczak B, van Diest PJ, Boecker W (2001) Ductal invasive G2 and G3 carcinomas of the breast are the end stages of at least two different lines of genetic evolution. J Pathol 194:165–170CrossRefPubMed Buerger H, Mommers EC, Littmann R, Simon R, Diallo R, Poremba C, Dockhorn-Dworniczak B, van Diest PJ, Boecker W (2001) Ductal invasive G2 and G3 carcinomas of the breast are the end stages of at least two different lines of genetic evolution. J Pathol 194:165–170CrossRefPubMed
8.
go back to reference Camp RL, Dolled-Filhart M, King BL, Rimm DL (2003) Quantitative analysis of breast cancer tissue microarrays shows that both high and normal levels of HER2 expression are associated with poor outcome. Cancer Res 63:1445–1448PubMed Camp RL, Dolled-Filhart M, King BL, Rimm DL (2003) Quantitative analysis of breast cancer tissue microarrays shows that both high and normal levels of HER2 expression are associated with poor outcome. Cancer Res 63:1445–1448PubMed
9.
go back to reference Early Breast Cancer Trialists’ Collaborative Group (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 365:1687–1717CrossRef Early Breast Cancer Trialists’ Collaborative Group (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 365:1687–1717CrossRef
10.
go back to reference Eiermann W, Rezai M, Kummel S, Kuhn T, Warm M, Friedrichs K, Schneeweiss A, Markmann S, Eggemann H, Hilfrich J, Jackisch C, Witzel I, Eidtmann H, Bachinger A, Hell S, Blohmer J (2013) The 21-gene recurrence score assay impacts adjuvant therapy recommendations for ER-positive, node-negative and node-positive early breast cancer resulting in a risk-adapted change in chemotherapy use. Ann Oncol 24:618–624CrossRefPubMedCentralPubMed Eiermann W, Rezai M, Kummel S, Kuhn T, Warm M, Friedrichs K, Schneeweiss A, Markmann S, Eggemann H, Hilfrich J, Jackisch C, Witzel I, Eidtmann H, Bachinger A, Hell S, Blohmer J (2013) The 21-gene recurrence score assay impacts adjuvant therapy recommendations for ER-positive, node-negative and node-positive early breast cancer resulting in a risk-adapted change in chemotherapy use. Ann Oncol 24:618–624CrossRefPubMedCentralPubMed
11.
go back to reference Gasparini G, Gullick WJ, Maluta S, Dalla PP, Caffo O, Leonardi E, Boracchi P, Pozza F, Lemoine NR, Bevilacqua P (1994) c-erbB-3 and c-erbB-2 protein expression in node-negative breast carcinoma–an immunocytochemical study. Eur J Cancer 30A:16–22CrossRefPubMed Gasparini G, Gullick WJ, Maluta S, Dalla PP, Caffo O, Leonardi E, Boracchi P, Pozza F, Lemoine NR, Bevilacqua P (1994) c-erbB-3 and c-erbB-2 protein expression in node-negative breast carcinoma–an immunocytochemical study. Eur J Cancer 30A:16–22CrossRefPubMed
12.
go back to reference Gennari A, Sormani MP, Pronzato P, Puntoni M, Colozza M, Pfeffer U, Bruzzi P (2008) HER2 status and efficacy of adjuvant anthracyclines in early breast cancer: a pooled analysis of randomized trials. J Natl Cancer Inst 100:14–20CrossRefPubMed Gennari A, Sormani MP, Pronzato P, Puntoni M, Colozza M, Pfeffer U, Bruzzi P (2008) HER2 status and efficacy of adjuvant anthracyclines in early breast cancer: a pooled analysis of randomized trials. J Natl Cancer Inst 100:14–20CrossRefPubMed
13.
go back to reference Gilcrease MZ, Woodward WA, Nicolas MM, Corley LJ, Fuller GN, Esteva FJ, Tucker SL, Buchholz TA (2009) Even low-level HER2 expression may be associated with worse outcome in node-positive breast cancer. Am J Surg Pathol 33:759–767CrossRefPubMedCentralPubMed Gilcrease MZ, Woodward WA, Nicolas MM, Corley LJ, Fuller GN, Esteva FJ, Tucker SL, Buchholz TA (2009) Even low-level HER2 expression may be associated with worse outcome in node-positive breast cancer. Am J Surg Pathol 33:759–767CrossRefPubMedCentralPubMed
14.
go back to reference Goldhirsch A, Wood WC, Gelber RD, Coates AS, Thurlimann B, Senn HJ (2007) Progress and promise: highlights of the international expert consensus on the primary therapy of early breast cancer 2007. Ann Oncol 18:1133–1144CrossRefPubMed Goldhirsch A, Wood WC, Gelber RD, Coates AS, Thurlimann B, Senn HJ (2007) Progress and promise: highlights of the international expert consensus on the primary therapy of early breast cancer 2007. Ann Oncol 18:1133–1144CrossRefPubMed
15.
go back to reference Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, Thurlimann B, Senn HJ (2013) Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol 24:2206–2223CrossRefPubMedCentralPubMed Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, Thurlimann B, Senn HJ (2013) Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol 24:2206–2223CrossRefPubMedCentralPubMed
16.
go back to reference Harris L, Fritsche H, Mennel R, Norton L, Ravdin P, Taube S, Somerfield MR, Hayes DF, Bast RC Jr (2007) American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol 25:5287–5312CrossRefPubMed Harris L, Fritsche H, Mennel R, Norton L, Ravdin P, Taube S, Somerfield MR, Hayes DF, Bast RC Jr (2007) American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol 25:5287–5312CrossRefPubMed
17.
go back to reference Iorfida M, Dellapasqua S, Bagnardi V, Cardillo A, Rotmensz N, Mastropasqua MG, Bottiglieri L, Goldhirsch A, Viale G, Colleoni M (2012) HER2−negative (1+) breast cancer with unfavorable prognostic features: to FISH or not to FISH? Ann Oncol 23:1371–1372CrossRefPubMed Iorfida M, Dellapasqua S, Bagnardi V, Cardillo A, Rotmensz N, Mastropasqua MG, Bottiglieri L, Goldhirsch A, Viale G, Colleoni M (2012) HER2−negative (1+) breast cancer with unfavorable prognostic features: to FISH or not to FISH? Ann Oncol 23:1371–1372CrossRefPubMed
18.
go back to reference Ivshina AV, George J, Senko O, Mow B, Putti TC, Smeds J, Lindahl T, Pawitan Y, Hall P, Nordgren H, Wong JE, Liu ET, Bergh J, Kuznetsov VA, Miller LD (2006) Genetic reclassification of histologic grade delineates new clinical subtypes of breast cancer. Cancer Res 66:10292–10301CrossRefPubMed Ivshina AV, George J, Senko O, Mow B, Putti TC, Smeds J, Lindahl T, Pawitan Y, Hall P, Nordgren H, Wong JE, Liu ET, Bergh J, Kuznetsov VA, Miller LD (2006) Genetic reclassification of histologic grade delineates new clinical subtypes of breast cancer. Cancer Res 66:10292–10301CrossRefPubMed
19.
go back to reference Jacobs TW, Gown AM, Yaziji H, Barnes MJ, Schnitt SJ (1999) Specificity of HercepTest in determining HER-2/neu status of breast cancers using the United States Food and Drug Administration-approved scoring system. J Clin Oncol 17:1983–1987PubMed Jacobs TW, Gown AM, Yaziji H, Barnes MJ, Schnitt SJ (1999) Specificity of HercepTest in determining HER-2/neu status of breast cancers using the United States Food and Drug Administration-approved scoring system. J Clin Oncol 17:1983–1987PubMed
20.
go back to reference Lee HJ, Seo AN, Kim EJ, Jang MH, Suh KJ, Ryu HS, Kim YJ, Kim JH, Im SA, Gong G, Jung KH, Park IA, Park SY (2014) HER2 heterogeneity affects trastuzumab responses and survival in patients with HER2−positive metastatic breast cancer. Am J Clin Pathol 142:755–766CrossRefPubMed Lee HJ, Seo AN, Kim EJ, Jang MH, Suh KJ, Ryu HS, Kim YJ, Kim JH, Im SA, Gong G, Jung KH, Park IA, Park SY (2014) HER2 heterogeneity affects trastuzumab responses and survival in patients with HER2−positive metastatic breast cancer. Am J Clin Pathol 142:755–766CrossRefPubMed
21.
go back to reference Look MP, van Putten WL, Duffy MJ, Harbeck N, Christensen IJ, Thomssen C, Kates R, Spyratos F, Ferno M, Eppenberger-Castori S, Sweep CG, Ulm K, Peyrat JP, Martin PM, Magdelenat H, Brunner N, Duggan C, Lisboa BW, Bendahl PO, Quillien V, Daver A, Ricolleau G, Meijer-van Gelder ME, Manders P, Fiets WE, Blankenstein MA, Broet P, Romain S, Daxenbichler G, Windbichler G, Cufer T, Borstnar S, Kueng W, Beex LV, Klijn JG, O’Higgins N, Eppenberger U, Janicke F, Schmitt M, Foekens JA (2002) Pooled analysis of prognostic impact of urokinase-type plasminogen activator and its inhibitor PAI-1 in 8377 breast cancer patients. J Natl Cancer Inst 94:116–128CrossRefPubMed Look MP, van Putten WL, Duffy MJ, Harbeck N, Christensen IJ, Thomssen C, Kates R, Spyratos F, Ferno M, Eppenberger-Castori S, Sweep CG, Ulm K, Peyrat JP, Martin PM, Magdelenat H, Brunner N, Duggan C, Lisboa BW, Bendahl PO, Quillien V, Daver A, Ricolleau G, Meijer-van Gelder ME, Manders P, Fiets WE, Blankenstein MA, Broet P, Romain S, Daxenbichler G, Windbichler G, Cufer T, Borstnar S, Kueng W, Beex LV, Klijn JG, O’Higgins N, Eppenberger U, Janicke F, Schmitt M, Foekens JA (2002) Pooled analysis of prognostic impact of urokinase-type plasminogen activator and its inhibitor PAI-1 in 8377 breast cancer patients. J Natl Cancer Inst 94:116–128CrossRefPubMed
22.
go back to reference Menard S, Balsari A, Tagliabue E, Camerini T, Casalini P, Bufalino R, Castiglioni F, Carcangiu ML, Gloghini A, Scalone S, Querzoli P, Lunardi M, Molino A, Mandara M, Mottolese M, Marandino F, Venturini M, Bighin C, Cancello G, Montagna E, Perrone F, De MA, Sapino A, Donadio M, Battelli N, Santinelli A, Pavesi L, Lanza A, Zito FA, Labriola A, Aiello RA, Caruso M, Zanconati F, Mustacchi G, Barbareschi M, Frisinghelli M, Russo R, Carrillo G (2008) Biology, prognosis and response to therapy of breast carcinomas according to HER2 score. Ann Oncol 19:1706–1712CrossRefPubMed Menard S, Balsari A, Tagliabue E, Camerini T, Casalini P, Bufalino R, Castiglioni F, Carcangiu ML, Gloghini A, Scalone S, Querzoli P, Lunardi M, Molino A, Mandara M, Mottolese M, Marandino F, Venturini M, Bighin C, Cancello G, Montagna E, Perrone F, De MA, Sapino A, Donadio M, Battelli N, Santinelli A, Pavesi L, Lanza A, Zito FA, Labriola A, Aiello RA, Caruso M, Zanconati F, Mustacchi G, Barbareschi M, Frisinghelli M, Russo R, Carrillo G (2008) Biology, prognosis and response to therapy of breast carcinomas according to HER2 score. Ann Oncol 19:1706–1712CrossRefPubMed
23.
go back to reference Minner S, Jessen B, Stiedenroth L, Burandt E, Kollermann J, Mirlacher M, Erbersdobler A, Eichelberg C, Fisch M, Brummendorf TH, Bokemeyer C, Simon R, Steuber T, Graefen M, Huland H, Sauter G, Schlomm T (2010) Low level HER2 overexpression is associated with rapid tumor cell proliferation and poor prognosis in prostate cancer. Clin Cancer Res 16:1553–1560CrossRefPubMed Minner S, Jessen B, Stiedenroth L, Burandt E, Kollermann J, Mirlacher M, Erbersdobler A, Eichelberg C, Fisch M, Brummendorf TH, Bokemeyer C, Simon R, Steuber T, Graefen M, Huland H, Sauter G, Schlomm T (2010) Low level HER2 overexpression is associated with rapid tumor cell proliferation and poor prognosis in prostate cancer. Clin Cancer Res 16:1553–1560CrossRefPubMed
24.
go back to reference Paik S, Hazan R, Fisher ER, Sass RE, Fisher B, Redmond C, Schlessinger J, Lippman ME, King CR (1990) Pathologic findings from the National Surgical Adjuvant Breast and Bowel Project: prognostic significance of erbB-2 protein overexpression in primary breast cancer. J Clin Oncol 8:103–112PubMed Paik S, Hazan R, Fisher ER, Sass RE, Fisher B, Redmond C, Schlessinger J, Lippman ME, King CR (1990) Pathologic findings from the National Surgical Adjuvant Breast and Bowel Project: prognostic significance of erbB-2 protein overexpression in primary breast cancer. J Clin Oncol 8:103–112PubMed
25.
go back to reference Paik S, Kim C, Wolmark N (2008) HER2 status and benefit from adjuvant trastuzumab in breast cancer. N Engl J Med 358:1409–1411CrossRefPubMed Paik S, Kim C, Wolmark N (2008) HER2 status and benefit from adjuvant trastuzumab in breast cancer. N Engl J Med 358:1409–1411CrossRefPubMed
26.
go back to reference Perez EA, Reinholz MM, Hillman DW, Tenner KS, Schroeder MJ, Davidson NE, Martino S, Sledge GW, Harris LN, Gralow JR, Dueck AC, Ketterling RP, Ingle JN, Lingle WL, Kaufman PA, Visscher DW, Jenkins RB (2010) HER2 and chromosome 17 effect on patient outcome in the N9831 adjuvant trastuzumab trial. J Clin Oncol 28:4307–4315CrossRefPubMedCentralPubMed Perez EA, Reinholz MM, Hillman DW, Tenner KS, Schroeder MJ, Davidson NE, Martino S, Sledge GW, Harris LN, Gralow JR, Dueck AC, Ketterling RP, Ingle JN, Lingle WL, Kaufman PA, Visscher DW, Jenkins RB (2010) HER2 and chromosome 17 effect on patient outcome in the N9831 adjuvant trastuzumab trial. J Clin Oncol 28:4307–4315CrossRefPubMedCentralPubMed
27.
go back to reference Rakha EA, Reis-Filho JS, Baehner F, Dabbs DJ, Decker T, Eusebi V, Fox SB, Ichihara S, Jacquemier J, Lakhani SR, Palacios J, Richardson AL, Schnitt SJ, Schmitt FC, Tan PH, Tse GM, Badve S, Ellis IO (2010) Breast cancer prognostic classification in the molecular era: the role of histological grade. Breast Cancer Res 12:207PubMedCentralPubMed Rakha EA, Reis-Filho JS, Baehner F, Dabbs DJ, Decker T, Eusebi V, Fox SB, Ichihara S, Jacquemier J, Lakhani SR, Palacios J, Richardson AL, Schnitt SJ, Schmitt FC, Tan PH, Tse GM, Badve S, Ellis IO (2010) Breast cancer prognostic classification in the molecular era: the role of histological grade. Breast Cancer Res 12:207PubMedCentralPubMed
28.
go back to reference Ross JS, Fletcher JA (1998) The HER-2/neu oncogene in breast cancer: prognostic factor, predictive factor, and target for therapy. Oncologist 3:237–252PubMed Ross JS, Fletcher JA (1998) The HER-2/neu oncogene in breast cancer: prognostic factor, predictive factor, and target for therapy. Oncologist 3:237–252PubMed
29.
go back to reference Rossi V, Sarotto I, Maggiorotto F, Berchialla P, Kubatzki F, Tomasi N, Redana S, Martinello R, Valabrega G, Aglietta M, Ponzone R, Montemurro F (2012) Moderate immunohistochemical expression of HER-2 (2+) without HER-2 gene amplification is a negative prognostic factor in early breast cancer. Oncologist 17:1418–1425CrossRefPubMedCentralPubMed Rossi V, Sarotto I, Maggiorotto F, Berchialla P, Kubatzki F, Tomasi N, Redana S, Martinello R, Valabrega G, Aglietta M, Ponzone R, Montemurro F (2012) Moderate immunohistochemical expression of HER-2 (2+) without HER-2 gene amplification is a negative prognostic factor in early breast cancer. Oncologist 17:1418–1425CrossRefPubMedCentralPubMed
30.
go back to reference Schmidt M, Victor A, Bratzel D, Boehm D, Cotarelo C, Lebrecht A, Siggelkow W, Hengstler JG, Elsasser A, Gehrmann M, Lehr HA, Koelbl H, von Minckwitz G, Harbeck N, Thomssen C (2009) Long-term outcome prediction by clinicopathological risk classification algorithms in node-negative breast cancer–comparison between Adjuvant!, St Gallen, and a novel risk algorithm used in the prospective randomized Node-Negative-Breast Cancer-3 (NNBC-3) trial. Ann Oncol 20:258–264CrossRefPubMed Schmidt M, Victor A, Bratzel D, Boehm D, Cotarelo C, Lebrecht A, Siggelkow W, Hengstler JG, Elsasser A, Gehrmann M, Lehr HA, Koelbl H, von Minckwitz G, Harbeck N, Thomssen C (2009) Long-term outcome prediction by clinicopathological risk classification algorithms in node-negative breast cancer–comparison between Adjuvant!, St Gallen, and a novel risk algorithm used in the prospective randomized Node-Negative-Breast Cancer-3 (NNBC-3) trial. Ann Oncol 20:258–264CrossRefPubMed
31.
go back to reference Seol H, Lee HJ, Choi Y, Lee HE, Kim YJ, Kim JH, Kang E, Kim SW, Park SY (2012) Intratumoral heterogeneity of HER2 gene amplification in breast cancer: its clinicopathological significance. Mod Pathol 25:938–948CrossRefPubMed Seol H, Lee HJ, Choi Y, Lee HE, Kim YJ, Kim JH, Kang E, Kim SW, Park SY (2012) Intratumoral heterogeneity of HER2 gene amplification in breast cancer: its clinicopathological significance. Mod Pathol 25:938–948CrossRefPubMed
32.
go back to reference Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235:177–182CrossRefPubMed Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235:177–182CrossRefPubMed
33.
go back to reference Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, Levin WJ, Stuart SG, Udove J, Ullrich A (1989) Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 244:707–712CrossRefPubMed Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, Levin WJ, Stuart SG, Udove J, Ullrich A (1989) Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 244:707–712CrossRefPubMed
34.
go back to reference von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP (2007) The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet 370:1453–1457CrossRef von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP (2007) The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet 370:1453–1457CrossRef
35.
go back to reference Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A, McShane LM, Paik S, Pegram MD, Perez EA, Press MF, Rhodes A, Sturgeon C, Taube SE, Tubbs R, Vance GH, van de Vijver M, Wheeler TM, Hayes DF (2007) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol 25:118–145CrossRefPubMed Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A, McShane LM, Paik S, Pegram MD, Perez EA, Press MF, Rhodes A, Sturgeon C, Taube SE, Tubbs R, Vance GH, van de Vijver M, Wheeler TM, Hayes DF (2007) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol 25:118–145CrossRefPubMed
36.
go back to reference Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, Allred DC, Bartlett JM, Bilous M, Fitzgibbons P, Hanna W, Jenkins RB, Mangu PB, Paik S, Perez EA, Press MF, Spears PA, Vance GH, Viale G, Hayes DF (2013) Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol 31:3997–4013CrossRefPubMed Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, Allred DC, Bartlett JM, Bilous M, Fitzgibbons P, Hanna W, Jenkins RB, Mangu PB, Paik S, Perez EA, Press MF, Spears PA, Vance GH, Viale G, Hayes DF (2013) Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol 31:3997–4013CrossRefPubMed
Metadata
Title
Moderate level of HER2 expression and its prognostic significance in breast cancer with intermediate grade
Authors
Tanja Ignatov
Holm Eggemann
Elke Burger
Franziska Fettke
Serban Dan Costa
Atanas Ignatov
Publication date
01-06-2015
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 2/2015
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-015-3407-2

Other articles of this Issue 2/2015

Breast Cancer Research and Treatment 2/2015 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine